Alzheimer Disease
Conditions
Brief summary
The purpose of this study is to test the safety, tolerability and the immune response to an investigational vaccine, V950, with or without ISCOMATRIX™ (IMX).
Interventions
BIOLOGICALV950
V950 will be given in doses of 0.5, 5 or 50 mcg depending on arm assignment.
BIOLOGICALISCOMATRIX™
ISCOMATRIX will be given in doses of 0, 16, 47 or 94 mcg depending on arm assignment.
BIOLOGICALPlacebo to V950
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has mild to moderate Alzheimer Disease * Women cannot be able to get pregnant * Patient has a reliable caregiver, who will attend all visits and answer questions about the patient
Exclusion criteria
* Patient lives in a nursing home or facility * Patient has another neurological or neurodegenerative disorder * Patient has a history of stroke * Patient uses illicit drugs or has a history of drug/alcohol abuse * Patient has received blood or blood derived products within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event | Up to 4 years after first dose of vaccine | An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 6 months after first dose of vaccine | This is a measure of the number of participants who discontinued study drug because of an adverse event. An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. |
| Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | Month 7 | The level of Aβ Peptide 1-40 specific antibodies was measured as the geometric mean titer (GMT) one month after the third dose (Month 7) of vaccine using an enzyme-linked immunosorbent assay (ELISA). |
| Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | Baseline and Month 7 | The Aβ Peptide 1-40 specific immunogenicity of 3-dose regimen of V950 was measured one month after the third dose (Month 7) of vaccine by the GMT fold change of Aβ 1-40 specific antibodies compared to Baseline (Month 0) using ELISA. |
Participant flow
Recruitment details
Participants were recruited from 51 sites in Europe, South America and the United States. The primary treatment period was from June 2007 to August 2010, with follow up through January 2012.
Participants by arm
| Arm | Count |
|---|---|
| Placebo to V950/IMX 0 mcg Participants receive Placebo to V950/IMX 0 mcg | 5 |
| Placebo to V950/IMX 16 mcg Participants receive Placebo to V950/IMX 16 mcg | 13 |
| V950 0.5 mcg/IMX 0 mcg Participants receive V950 0.5 mcg/IMX 0 mcg | 8 |
| V950 0.5 mcg/IMX 16 mcg Participants receive V950 0.5 mcg/IMX 16 mcg | 8 |
| V950 0.5 mcg/IMX 47 mcg Participants receive V950 0.5 mcg/IMX 47 mcg | 7 |
| V950 0.5 mcg/IMX 94 mcg Participants receive V950 0.5 mcg/IMX 94 mcg | 7 |
| V950 5 mcg/IMX 0 mcg Participants receive V950 5 mcg/IMX 0 mcg | 9 |
| V950 5 mcg/IMX 16 mcg Participants receive V950 5 mcg/IMX 16 mcg | 8 |
| V950 5 mcg/IMX 47 mcg Participants receive V950 5 mcg/IMX 47 mcg | 8 |
| V950 50 mcg/IMX 0 mcg Participants receive V950 50 mcg/IMX 0 mcg | 5 |
| V950 50 mcg/IMX 16 mcg Participants receive V950 50 mcg/IMX 16 mcg | 8 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 2 | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 7 | 4 | 2 | 2 | 2 | 2 | 1 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo to V950/IMX 0 mcg | Placebo to V950/IMX 16 mcg | V950 0.5 mcg/IMX 0 mcg | V950 0.5 mcg/IMX 16 mcg | V950 0.5 mcg/IMX 47 mcg | V950 0.5 mcg/IMX 94 mcg | V950 5 mcg/IMX 0 mcg | V950 5 mcg/IMX 16 mcg | V950 5 mcg/IMX 47 mcg | V950 50 mcg/IMX 0 mcg | V950 50 mcg/IMX 16 mcg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 73.6 years STANDARD_DEVIATION 10.69 | 70.7 years STANDARD_DEVIATION 9.6 | 76.9 years STANDARD_DEVIATION 4.39 | 73.6 years STANDARD_DEVIATION 8.07 | 76.1 years STANDARD_DEVIATION 8.01 | 73.4 years STANDARD_DEVIATION 10.89 | 72.6 years STANDARD_DEVIATION 9.26 | 72.5 years STANDARD_DEVIATION 10.1 | 81.5 years STANDARD_DEVIATION 5.48 | 70.6 years STANDARD_DEVIATION 8.38 | 75.5 years STANDARD_DEVIATION 10.04 | 74.2 years STANDARD_DEVIATION 8.85 |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 3 Participants | 5 Participants | 5 Participants | 6 Participants | 4 Participants | 5 Participants | 1 Participants | 3 Participants | 3 Participants | 45 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 5 Participants | 3 Participants | 2 Participants | 1 Participants | 5 Participants | 3 Participants | 7 Participants | 2 Participants | 5 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 5 | 11 / 13 | 7 / 8 | 8 / 8 | 6 / 7 | 7 / 7 | 9 / 9 | 8 / 8 | 8 / 8 | 5 / 5 | 8 / 8 |
| serious Total, serious adverse events | 1 / 5 | 0 / 13 | 2 / 8 | 2 / 8 | 3 / 7 | 1 / 7 | 4 / 9 | 1 / 8 | 2 / 8 | 1 / 5 | 0 / 8 |
Outcome results
Primary
Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7
The level of Aβ Peptide 1-40 specific antibodies was measured as the geometric mean titer (GMT) one month after the third dose (Month 7) of vaccine using an enzyme-linked immunosorbent assay (ELISA).
Time frame: Month 7
Population: Population consists of all participants who received three doses of vaccine and had no protocol violations. No participants in the V950 50 mcg/IMX 0 mcg group had data for the Month 7 evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo to V950/ IMX 0 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 363 ng/mL |
| Placebo to V950/ IMX 16 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 542.08 ng/mL |
| V950 0.5 mcg / IMX 0 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 855 ng/mL |
| V950 0.5 mcg / IMX 16 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 443 ng/mL |
| V950 0.5 mcg / IMX 47 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 990 ng/mL |
| V950 0.5 mcg / IMX 94 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 2208.02 ng/mL |
| V950 5 mcg / IMX 0 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 725 ng/mL |
| V950 5 mcg / IMX 16 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 3835 ng/mL |
| V950 5 mcg / IMX 47 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 1277.38 ng/mL |
| V950 50 mcg / IMX 16 mcg | Geometric Mean Titer (GMT) of Amyloid Beta (Aβ) Peptide 1-40 Specific Antibodies at Month 7 | 935.55 ng/mL |
Primary
Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies
The Aβ Peptide 1-40 specific immunogenicity of 3-dose regimen of V950 was measured one month after the third dose (Month 7) of vaccine by the GMT fold change of Aβ 1-40 specific antibodies compared to Baseline (Month 0) using ELISA.
Time frame: Baseline and Month 7
Population: Population consists of all participants who received three doses of vaccine and had no protocol violations. No participants in the V950 50 mcg/IMX 0 mcg group had data for the Month 7 evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo to V950/ IMX 0 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 0.89 fold change |
| Placebo to V950/ IMX 16 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 0.76 fold change |
| V950 0.5 mcg / IMX 0 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 0.98 fold change |
| V950 0.5 mcg / IMX 16 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 1.02 fold change |
| V950 0.5 mcg / IMX 47 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 0.15 fold change |
| V950 0.5 mcg / IMX 94 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 2.68 fold change |
| V950 5 mcg / IMX 0 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 0.74 fold change |
| V950 5 mcg / IMX 16 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 2.27 fold change |
| V950 5 mcg / IMX 47 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 1.38 fold change |
| V950 50 mcg / IMX 16 mcg | Mean Fold Change From Baseline in GMT of Aβ Peptide 1-40 Specific Antibodies | 1.84 fold change |
Primary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
This is a measure of the number of participants who discontinued study drug because of an adverse event. An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Time frame: Up to 6 months after first dose of vaccine
Population: Population consists of all participants who received at least one dose of vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo to V950/ IMX 0 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| Placebo to V950/ IMX 16 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| V950 0.5 mcg / IMX 0 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| V950 0.5 mcg / IMX 16 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 participants |
| V950 0.5 mcg / IMX 47 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 participants |
| V950 0.5 mcg / IMX 94 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| V950 5 mcg / IMX 0 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 participants |
| V950 5 mcg / IMX 16 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| V950 5 mcg / IMX 47 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 3 participants |
| V950 50 mcg / IMX 0 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 participants |
| V950 50 mcg / IMX 16 mcg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 2 participants |
Primary
Number of Participants Who Experienced at Least One Adverse Event
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Time frame: Up to 4 years after first dose of vaccine
Population: Population consists of all participants who received at least one dose of vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo to V950/ IMX 0 mcg | Number of Participants Who Experienced at Least One Adverse Event | 4 participants |
| Placebo to V950/ IMX 16 mcg | Number of Participants Who Experienced at Least One Adverse Event | 11 participants |
| V950 0.5 mcg / IMX 0 mcg | Number of Participants Who Experienced at Least One Adverse Event | 7 participants |
| V950 0.5 mcg / IMX 16 mcg | Number of Participants Who Experienced at Least One Adverse Event | 8 participants |
| V950 0.5 mcg / IMX 47 mcg | Number of Participants Who Experienced at Least One Adverse Event | 6 participants |
| V950 0.5 mcg / IMX 94 mcg | Number of Participants Who Experienced at Least One Adverse Event | 7 participants |
| V950 5 mcg / IMX 0 mcg | Number of Participants Who Experienced at Least One Adverse Event | 9 participants |
| V950 5 mcg / IMX 16 mcg | Number of Participants Who Experienced at Least One Adverse Event | 8 participants |
| V950 5 mcg / IMX 47 mcg | Number of Participants Who Experienced at Least One Adverse Event | 8 participants |
| V950 50 mcg / IMX 0 mcg | Number of Participants Who Experienced at Least One Adverse Event | 5 participants |
| V950 50 mcg / IMX 16 mcg | Number of Participants Who Experienced at Least One Adverse Event | 8 participants |